Abstract

Purpose. In this study, we developed and evaluated a novel method to produce insulin-loaded hydrophilic microspheres allowing high encapsulation efficiency and the preservation of peptide stability during particle processing. The preparation method used the diffusion of water by an excess of solvent starting from a water-in-solvent emulsion.

Methods. The water dispersed phase containing albumin or lactose, or albumin-lactose in different weight ratios, and insulin was emulsified in water-saturated triacetin with and without emulsifiers, producing a water-in-triacetin emulsion. An excess of triacetin was added to the emulsion so that water could be extracted into the continuous phase, allowing the insulin-loaded microsphere precipitation. Insulin stability within the microspheres after processing was evaluated by reverse-phase and size-exclusion high-performance liquid chromatography.

Results. The water diffusion extraction process provided spherical microparticles of albumin or albumin-lactose. The mean diameter of the microspheres prepared with or without emulsifiers ranged from 2 to 10 μm, and the encapsulation efficiency of insulin was between 60% and 75%, respectively. The analysis of microsphere content after processing showed that insulin did not undergo any chemical modification within microspheres. The use of lactose alone led to the formation of highly viscous droplets that coalesced during the purification step.

Conclusions. The water extraction procedures successfully produced insulin-loaded hydrophilic microspheres allowing the preservation of peptide stability. The type of excipient and the size of the disperse phase of the primary w/o emulsion were crucial determinants of microsphere characteristics.